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Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation

Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu exc...

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Autores principales: Rivero-Segura, Nadia A., Flores-Soto, Edgar, García de la Cadena, Selene, Coronado-Mares, Isabel, Gomez-Verjan, Juan C., Ferreira, Diana G., Cabrera-Reyes, Erika Alejandra, Lopes, Luísa V., Massieu, Lourdes, Cerbón, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419567/
https://www.ncbi.nlm.nih.gov/pubmed/28475602
http://dx.doi.org/10.1371/journal.pone.0176910
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author Rivero-Segura, Nadia A.
Flores-Soto, Edgar
García de la Cadena, Selene
Coronado-Mares, Isabel
Gomez-Verjan, Juan C.
Ferreira, Diana G.
Cabrera-Reyes, Erika Alejandra
Lopes, Luísa V.
Massieu, Lourdes
Cerbón, Marco
author_facet Rivero-Segura, Nadia A.
Flores-Soto, Edgar
García de la Cadena, Selene
Coronado-Mares, Isabel
Gomez-Verjan, Juan C.
Ferreira, Diana G.
Cabrera-Reyes, Erika Alejandra
Lopes, Luísa V.
Massieu, Lourdes
Cerbón, Marco
author_sort Rivero-Segura, Nadia A.
collection PubMed
description Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca(2+)] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca(2+)]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases.
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spelling pubmed-54195672017-05-14 Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation Rivero-Segura, Nadia A. Flores-Soto, Edgar García de la Cadena, Selene Coronado-Mares, Isabel Gomez-Verjan, Juan C. Ferreira, Diana G. Cabrera-Reyes, Erika Alejandra Lopes, Luísa V. Massieu, Lourdes Cerbón, Marco PLoS One Research Article Prolactin (PRL) is a peptidic hormone that displays pleiotropic functions in the organism including different actions in the brain. PRL exerts a neuroprotective effect against excitotoxicity produced by glutamate (Glu) or kainic acid in both in vitro and in vivo models. It is well known that Glu excitotoxicity causes cell death through apoptotic or necrotic pathways due to intracellular calcium ([Ca(2+)] i) overload. Therefore, the aim of the present study was to assess the molecular mechanisms by which PRL maintains cellular viability of primary cultures of rat hippocampal neurons exposed to Glu excitotoxicity. We determined cell viability by monitoring mitochondrial activity and using fluorescent markers for viable and dead cells. The intracellular calcium level was determined by a fluorometric assay and proteins involved in the apoptotic pathway were determined by immunoblot. Our results demonstrated that PRL afforded neuroprotection against Glu excitotoxicity, as evidenced by a decrease in propidium iodide staining and by the decrease of the LDH activity. In addition, the MTT assay shows that PRL maintains normal mitochondrial activity even in neurons exposed to Glu. Furthermore, the Glu-induced intracellular [Ca(2+)]i overload was attenuated by PRL. These data correlate with the reduction found in the level of active caspase-3 and the pro-apoptotic ratio (Bax/Bcl-2). Concomitantly, PRL elicited the nuclear translocation of the transcriptional factor NF-κB, which was detected by immunofluorescence and confocal microscopy. To our knowledge, this is the first report demonstrating that PRL prevents Glu excitotoxicity by a mechanism involving the restoration of the intracellular calcium homeostasis and mitochondrial activity, as well as an anti-apoptotic action possibly mediated by the activity of NF-κB. Overall, the current results suggest that PRL could be of potential therapeutic advantage in the treatment of neurodegenerative diseases. Public Library of Science 2017-05-05 /pmc/articles/PMC5419567/ /pubmed/28475602 http://dx.doi.org/10.1371/journal.pone.0176910 Text en © 2017 Rivero-Segura et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rivero-Segura, Nadia A.
Flores-Soto, Edgar
García de la Cadena, Selene
Coronado-Mares, Isabel
Gomez-Verjan, Juan C.
Ferreira, Diana G.
Cabrera-Reyes, Erika Alejandra
Lopes, Luísa V.
Massieu, Lourdes
Cerbón, Marco
Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation
title Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation
title_full Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation
title_fullStr Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation
title_full_unstemmed Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation
title_short Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca(2+)]i overload and NF-κB activation
title_sort prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [ca(2+)]i overload and nf-κb activation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419567/
https://www.ncbi.nlm.nih.gov/pubmed/28475602
http://dx.doi.org/10.1371/journal.pone.0176910
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